Citing Etsuko Ichihara as her inspiration, in 1989, Shishido decided to audition for a contest hosted by Lotte through the encouragement of her mother.[1] At the age of 16, she was selected as the winner out of 85,000 contestants[1] and appeared on their television commercial in the following year. Her first single, titled "Cosmic Rendezvous" (コズミック・ランデブー,Kozumikku Randebū), was released in 1990. Known by her idol nickname "Run Run" (るんるん,Run Run), she also joined the members of Lip's and Rakutenshi to form the short-lived idol group Nanatsuboshi as a side project. During her time as an idol, Shishido faced strict regulations during public appearances and was not allowed to speak out of turn, nor was she allowed to befriend other idols from rival managements.[1]

In 1992, Shishido, then 18 years old, terminated her contract, citing interest in other career paths such as acting and film.[1] She continued her singing career as an independent singer.[2] Her first indies album, Set Me Free, released in 1995 and had cost 500,000 yen to produce.[1] Her album was positively received, and Neil Strauss of The New York Times compared her "ripe, melodic voice" to Debbie Gibson and Liz Phair.[3]

Since meeting guitarist Kohei Shigihara, most of Shishido's music has been composed by him.[4] The first song produced by the two was titled "Lion to Kyūka" (ライオンと休暇,Raion to Kyūka) in 2006,[5] which Shishido describes as the song "[seeming] to have been [her] image" and that "[t]hough [she is] refreshing, [she sings] the sense of the vanity of life of the man and woman".[5]

On May 9, 2010, Shishido celebrated her 20th year anniversary in the music industry with a commemorative performance that was streamed live on Ustream. Her performance set a record of having the most people view her video on the entire history of the website.[4]

Shishido's first start at a voice acting career was in 1992, when she voiced Uni Charm Password from the OVA series of KO Beast. In 1995, she broke through with her first leading role as Mikako Kōda from Neighborhood Story and was encouraged to audition after producer Hiromi Seki had heard her speaking voice through her album, Do-Re-Mi-Fa-So-La-Ti-Do-Shi-Shi-Do-Ru-Mi.[1] Later, despite failing her audition for Doremi in Ojamajo Doremi, Shishido was later cast as Onpu, a role that boosted her popularity as a voice actress.[1]